{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:46Z","timestamp":1788844246661,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016247","name":"Wroc\u0142aw University of Environmental and Life Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016247","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05cs8k179","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Enantiomerically enriched vanillin-derived cis- and trans-\u03b2-aryl-\u03b4-iodo-\u03b3-lactones were synthesized using a chemoenzymatic pathway based on Candida antarctica lipase B (CALB)-catalyzed transesterification of racemic (E)-4-(4\u2032-benzyloxy-3\u2032-methoxyphenyl)but-3-en-2-ol, followed by Claisen rearrangement, hydrolysis, iodolactonization, and deprotection. The trans orientation of substituents on the \u03b3-lactone ring of the target compounds was identified as the key structural feature enhancing cell-viability-reducing activity against selected human cancer cell lines. No statistically significant differences were observed between the enantiomerically enriched pairs of the studied lactones: the most active trans-\u03b4-iodo-\u03b3-lactones, 7b, exhibited similarly high potency (IC50 = 3.98 \u00b1 2.60 \u03bcM and 5.08 \u00b1 1.30 \u03bcM) against the multidrug-resistant (MDR) gastric adenocarcinoma cell line EPG85-257RDB. Their IC50 values were not significantly different from that determined for doxorubicin under the same experimental conditions (IC50 = 5.48 \u00b1 0.75 \u03bcM). Notably, both enantiomers exhibited high selectivity indices (SI = 9.22 and 10.19, respectively). TUNEL analysis demonstrated that enantiomer (4R,5S,6R)-7b induced concentration-dependent DNA fragmentation, increasing the percentage of TUNEL-positive cells from 8.30 \u00b1 0.95% to 74.10 \u00b1 4.26%. Flow cytometric analysis further revealed the pronounced accumulation of cells in the G2\/M phase, with up to 55.25 \u00b1 2.74% of cells detected at the highest tested concentration. The observed activity of enantiomerically enriched vanillin-derived trans-\u03b2-aryl-\u03b4-iodo-\u03b3-lactone 7b in the multidrug-resistant EPG85-257RDB cell line warrants its further investigation in additional drug-resistant cancer models.<\/jats:p>","DOI":"10.3390\/ijms27177928","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"7928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Chemoenzymatic Synthesis to Biological Effects: Enantiomerically Enriched Vanillin-Derived \u03b4-Iodo-\u03b3-Lactones as Modulators of Cancer Cell Viability and Inducers of Cell Death"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4053-7721","authenticated-orcid":false,"given":"Anna","family":"Dunal","sequence":"first","affiliation":[{"name":"Department of Food Chemistry and Biocatalysis, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4296-3174","authenticated-orcid":false,"given":"Dominik","family":"Poradowski","sequence":"additional","affiliation":[{"name":"Department of Biostructure and Animal Physiology, Division of Animal Anatomy, Faculty of Veterinary Medicine, Wroc\u0142aw University of Environmental and Life Sciences, Ko\u017cuchowska 1, 51-631 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-8384","authenticated-orcid":false,"given":"Stefano","family":"Serra","sequence":"additional","affiliation":[{"name":"Consiglio Nazionale delle Ricerche (C.N.R.), Istituto di Scienze e Tecnologie Chimiche, Via Mancinelli 7, 20131 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9079-549X","authenticated-orcid":false,"given":"Aleksander","family":"Chr\u00f3szcz","sequence":"additional","affiliation":[{"name":"Department of Biostructure and Animal Physiology, Division of Animal Anatomy, Faculty of Veterinary Medicine, Wroc\u0142aw University of Environmental and Life Sciences, Ko\u017cuchowska 1, 51-631 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5229-4299","authenticated-orcid":false,"given":"Hanna","family":"Pruchnik","sequence":"additional","affiliation":[{"name":"Department of Physics and Biophysics, Faculty of Biotechnology and Food Sciences, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3271-779X","authenticated-orcid":false,"given":"Witold","family":"G\u0142adkowski","sequence":"additional","affiliation":[{"name":"Department of Food Chemistry and Biocatalysis, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/S0140-6736(25)01635-6","article-title":"The global, Regional, and National Burden of Cancer, 1990\u20132023, with Forecasts to 2050: A Systematic Analysis for the Global Burden of Disease Study 2023","volume":"406","author":"Force","year":"2025","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1016\/S0140-6736(25)01570-3","article-title":"Global Cancer Burden: Progress, Projections, and Challenges","volume":"406","author":"Luo","year":"2025","journal-title":"Lancet"},{"key":"ref_3","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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